Role of structural barriers in the mechanism of alternans-induced reentry.

Previously, using an animal model of T-wave alternans in structurally normal myocardium, we demonstrated that repolarization can alternate with opposite phase between neighboring myocytes (ie, discordant alternans), causing spatial dispersions of repolarization that form the substrate for functional block and reentrant ventricular fibrillation (VF). However, the mechanisms responsible for cellular discordant alternans and its electrocardiographic manifestation (ie, T-wave alternans) in patients with structural heart disease are unknown. We hypothesize that electrotonic uncoupling between neighboring regions of cells by a structural barrier (SB) is a mechanism for discordant alternans. Using voltage-sensitive dyes, ventricular action potentials were recorded from 26 Langendorff-perfused guinea pig hearts in the absence (ie, control) and presence of an insulating SB produced by an epicardial laser lesion. Quantitative analysis of magnitude and phase of cellular alternans revealed that in controls, action potential duration alternated in phase at all ventricular sites above a critical heart rate (269+/-17 bpm), ie, concordant alternans. Also, above a faster critical heart rate threshold (335+/-24 bpm), action potential duration alternated with opposite phase between sites, ie, discordant alternans. In contrast, only discordant but not concordant alternans was observed in 80% of hearts with the SB, and discordant alternans always occurred at a significantly slower heart rate (by 68+/-28 bpm) compared with controls. Therefore, the SB had a major effect on the alternans-heart rate relation, which served to facilitate the development of discordant alternans. Whether a SB was present or not, discordant alternans produced considerable increases (by approximately 170%) in the maximum spatial gradient of repolarization, which in turn formed the substrate for unidirectional block and reentry. However, by providing a structural anchor for stable reentry, discordant alternans in the presence of a SB led most often to sustained monomorphic ventricular tachycardia rather than to VF, whereas in the absence of a SB discordant alternans caused VF. SBs facilitate development of discordant alternans between cells with different ionic properties by electrotonically uncoupling neighboring regions of myocardium. This may explain why arrhythmia-prone patients with structural heart disease exhibit T-wave alternans at lower heart rates. These data also suggest a singular mechanism by which T-wave alternans forms a substrate for initiation of both VF and sustained monomorphic ventricular tachycardia.